Project Summary The ability to coordinate movements of the limbs is one of the main features of locomotion in mammals. Interlimb coordination is essential for maintaining balance when navigating in complex and/or changing environments. It involves complex dynamic interactions between neural circuits at different levels of the nervous system and biomechanical properties of the musculoskeletal system to allow animals to adjust locomotor speed and gait for goal-oriented behaviors. Interactions within the nervous system include those between the spinal circuits controlling each limb, supraspinal inputs and sensory feedback from the limbs. Neurological disorders resulting from spinal cord injury (SCI) and other diseases disrupt limb coordination in humans and animal models, thus impairing locomotion. Despite their obvious importance, the mechanisms that control interlimb coordination and contribute to locomotor recovery following SCI and other neurological disorders remain poorly understood. To address this gap in knowledge, we will integrate multiple experimental and modeling approaches to investigate the neural and biomechanical mechanisms controlling interlimb coordination in a feline model before and after SCI disrupting neural communication between the brain and spinal cord and/or between the circuits controlling fore- and hindlimb movements. The project will be performed in close interactive collaboration between three groups of investigators with strong and complementary expertise in the experimental study of cat locomotion, including SCI models (Alain Frigon, Universit de Sherbrooke), biomechanics of cat locomotion (Boris Prilutsky, Georgia Tech) and neural control of locomotion (Ilya Rybak, Drexel University). The project has the following Specific Aims: (1) Characterize muscle synergies and limb kinematics in intact and spinal cats during locomotion on regular and split-belt treadmills; (2) Extend and refine the current computational model of neural circuits and spinal central pattern generators involved in the control of locomotion; (3) Develop an integrated quadrupedal neuromechanical model of cat locomotion Develop an integrated quadrupedal neuromechanical model of cat locomotion; (4) Investigate the neural and biomechanical control of interlimb coordination during locomotion using interrelated and complementary experimental and modeling studies. Results obtained from these studies will have an important theoretical impact on our understanding of how the limbs are coordinated during locomotion and how this coordination is altered and adjusted after disruption of spinal pathways between left-right or cervical-lumbar circuits. The results will identify neural pathways and biomechanical mechanisms that could be targeted to improve interlimb coordination in people with various movement disorders, such as SCI, stroke, and Parkinson's disease.